Medical Summary
SarCNU (2-chloroethyl-3-sarcosinamide-1-nitrosourea, NSC364432) is a novel chloroethylnitrosourea which demonstrates selective cytotoxicity against primary human gliomas in vitro in the human tumor cloning assay and in-vivo efficacy against human glioma xenografts as compared to BCNU, the standard CNU utilized in the treatment of gliomas. The selective cytotoxicity of SarCNU in the human glioma cell line, SKMG-1, is associated with increased intracellular drug accumulation secondary to transport via the extraneuronal catecholamine uptake2 carrier. SarCNU is representative of a potentially new class of anticancer agents that displays increased antitumor activity by exploiting a physiological aspect of the tumor cell.

1. To define the maximum tolerated dose (MTD) of SarCNU administered orally on Days 1,5 and 9 every 4 weeks. (The day 1 dose of the initial cycle will be given intravenously over 1 hour for comparative pharmacokinetic studies).
2. To describe the toxicities of SarCNU with this schedule of administration.
3. To characterize the pharmacokinetics of SarCNU on this schedule.
4. To look for any evidence of antineoplastic activity of SarCNU

Lay Summary
This is a phase I study designed to examine the toxicity, pharmacology and possible clinical benefits of a new drug called SarCNU. The drug was initially developed at the Lady Davis Research Institute, and then was studied extensively at the U.S. National Cancer Institute, where it's anti-tumor effects in animals, as well as toxic side effects in animals were well characterized. In these models it works better than earlier versions of similar drugs, possibly because it is taken up into the tumor cells by a transport system that may be more abundant in cancer cells. It is very well absorbed after taking it as an oral pill. Except for the first dose, which will be an intravenous injection, the rest of the treatment will be in pill form. Patients are to be in the Clinical Research Unit to provide blood tests to measure the levels of the drug in their system at various times after drug administration. The classical model for phase I studies described in the "Clinical Research" section will be used. Patients may have had one previous type of chemotherapy, must be fully ambulatory, and have good kidney and liver function.

1. Histologic confirmation of an incurable solid tumor malignancy
2. No known standard therapy for the patient's disease that is potentially curative or definitely capable of extending life expectancy.
3. ECOG PS of 0, 1, or 2, with no recent weight loss of >10% of actual body weight.
4. Age >(or greater) 18 years.
5. Laboratory values (performed within 14 days prior to registration):
   - absolute neutrophil count >1500/µL;
   - hemoglobin >8 g/dL
   - either a creatinine < 1.5mg/dl or a creatinine clearance > 60 ml/min
   - a normal bilirubin
   - hepatic transaminase values < 2.5 x the upper limit of normal
   - baseline DLCO and vital capacity >80% of predicted
6. Oral intake > (or greater) 1,200 calories per/day.
7. Willingness to return for follow up.
8. Life expectancy of >12 weeks.
9. Patients must be fully informed about their illness and the investigational nature of the study protocol (including foreseeable risks and possible side effects) and must sign an informed consent.
10. None of the following prior therapies:
    - chemotherapy within the last 4 weeks.
    - prior nitrosourea therapy /mitomycin-C within the last 6 weeks.
    - biologic therapy within 4 weeks.
    - radiation therapy within 3 weeks of planned treatment with SarCNU, or radiation to >25% of bone marrow.
11. HIV negative patients because these patients are more likely to have severe toxicity.
12. Cannot have history of uncontrolled cardiac disease.
13. No pregnant or lactating women can be included, as SarCNU has not been tested in pregnancy and may pose a risk to the fetus, and potential excretion of SarCNU in breast milk has not been evaluated and may pose a serious risk to a breast fed infant.
14. Men and women of reproductive potential must have adequate contraception.
15. CNS metastases or history of CNS metastasis. Patients with primary CNS tumors are eligible if they are on a stable dose of steroids at least 2 weeks prior to entry.
16. There can be no serious intercurrent illnesses such as uncontrolled hypertension, uncontrolled infection or myelodysplastic syndrome; no recent major surgery (within 21 days).
17. No intercurrent radiation, chemotherapy, immunotherapy or hormonal therapy.